The achievement gap is a disparity in academic and standardized test performance that exists between White and underrepresented minority (URM) students that begins as early as preschool and worsens as students progress through the educational system. Medical education is not immune to this inequality. URM medical students are more likely to experience delayed graduation and course failure, even after accounting for science grade point average and Medical College Admission Test performance. Moreover, URM students are more likely to earn lower scores on licensing examinations, which can have a significant impact on their career trajectory, including specialty choice and residency competitiveness. After the release of preliminary recommendations from the Invitational Conference on USMLE Scoring (InCUS) and public commentary on these recommendations, the National Board of Medical Examiners and Federation of State Medical Boards announced that the United States Medical Licensing Examination (USMLE) Step 1 would transition from a 3-digit numeric score to pass/fail scoring. Given that another of InCUS’s recommendations was to “minimize racial demographic differences that exist in USMLE performance,” it is paramount to consider the impact of this scoring change on URM medical students specifically. Holistic admissions are a step in the right direction of acknowledging that URM students often travel a further distance to reach medical school. However, when residency programs emphasize USMLE performance (or any standardized test score) despite persistent test score gaps, medical education contributes to the disproportionate harm URM students face and bolsters segregation across medical specialties. This Perspective provides a brief explanation of the achievement gap, its psychological consequences, and its consequences in medical education; discusses the potential effect of the Step 1 scoring change on URM medical students; and provides a review of strategies to redress this disparity.

Target organ damage (TOD) manifests as vascular injuries in the body organ systems associated with long-standing hypertension. DNA methylation in peripheral blood leukocytes can capture inflammatory processes and gene expression changes underlying TOD. We investigated the association between epigenome-wide DNA methylation and five measures of TOD (estimated glomerular filtration rate (eGFR), urinary albumin-creatinine ratio (UACR), left ventricular mass index (LVMI), relative wall thickness (RWT), and white matter hyperintensity (WMH)) in 961 African Americans from hypertensive sibships. A multivariate (multi-trait) model of eGFR, UACR, LVMI, and RWT identified seven CpGs associated with at least one of the traits (cg21134922, cg04816311 near C7orf50, cg09155024, cg10254690 near OAT, cg07660512, cg12661888 near IFT43, and cg02264946 near CATSPERD) at FDR q < 0.1. Adjusting for blood pressure, body mass index, and type 2 diabetes attenuated the association for four CpGs. DNA methylation was associated with cis-gene expression for some CpGs, but no significant mediation by gene expression was detected. Mendelian randomization analyses suggested causality between three CpGs and eGFR (cg04816311, cg10254690, and cg07660512). We also assessed whether the identified CpGs were associated with TOD in 614 African Americans in the Hypertension Genetic Epidemiology Network (HyperGEN) study. Out of three CpGs available for replication, cg04816311 was significantly associated with eGFR (p = 0.0003), LVMI (p = 0.0003), and RWT (p = 0.002). This study found evidence of an association between DNA methylation and TOD in African Americans and highlights the utility of using a multivariate-based model that leverages information across related traits in epigenome-wide association studies.

Purpose: Compared with their European American (EA) counterparts, African American (AA) women are more likely to die from breast cancer in the United States. This disparity is greatest in hormone receptor–positive subtypes. Here we uncover biological factors underlying this disparity by comparing functional expression and prognostic significance of master transcriptional regulators of luminal differentiation. Experimental Design: Data and biospecimens from 262 AA and 293 EA patients diagnosed with breast cancer from 2001 to 2010 at a major medical center were analyzed by IHC for functional biomarkers of luminal differentiation, including estrogen receptor (ESR1) and its pioneer factors, FOXA1 and GATA3. Integrated comparison of protein levels with network-level gene expression analysis uncovered predictive correlations with race and survival. Results: Univariate or multivariate HRs for overall survival, estimated from digital IHC scoring of nuclear antigen, show distinct differences in the magnitude and significance of these biomarkers to predict survival based on race: ESR1 [EA HR = 0.47; 95% confidence interval (CI), 0.31–0.72 and AA HR = 0.77; 95% CI, 0.48–1.18]; FOXA1 (EA HR = 0.38; 95% CI, 0.23–0.63 and AA HR = 0.53; 95% CI, 0.31–0.88), and GATA3 (EA HR = 0.36; 95% CI, 0.23–0.56; AA HR = 0.57; CI, 0.56–1.4). In addition, we identify genes in the downstream regulons of these biomarkers highly correlated with race and survival. Conclusions: Even within clinically homogeneous tumor groups, regulatory networks that drive mammary luminal differentiation reveal race-specific differences in their association with clinical outcome. Understanding these biomarkers and their downstream regulons will elucidate the intrinsic mechanisms that drive racial disparities in breast cancer survival.

An estimated 250 million people worldwide suffer from knee osteoarthritis (KOA), with older adults having greater risk. Like other age-related diseases, residents of high-deprivation neighborhoods experience worse KOA pain outcomes compared to their more affluent neighbors. The purpose of this study was to examine the relationship between neighborhood deprivation and pain severity in KOA and the influence of epigenetic age acceleration (EpAA) on that relationship. The sample of 128 participants was mostly female (60.9%), approximately half non-Hispanic Black (49.2%), and had a mean age of 58 years. Spearman bivariate correlations revealed that pain severity positively correlated with EpAA (ρ = 0.47, p ≤ 0.001) and neighborhood deprivation (ρ = 0.25, p = 0.004). We found a positive significant relationship between neighborhood deprivation and EpAA (ρ = 0.47, p ≤ 0.001). Results indicate a mediating relationship between neighborhood deprivation (predictor), EpAA (mediator), and pain severity (outcome variable). There was a significant indirect effect of neighborhood deprivation on pain severity through EpAA, as the mediator accounted for a moderate portion of the total effect, PM = 0.44. Epigenetic age acceleration may act as a mechanism through which neighborhood deprivation leads to worse KOA pain outcomes and may play a role in the well-documented relationship between the neighborhood of residence and age-related diseases.